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dc.contributor.authorBoroughs, Angela C
dc.contributor.authorLarson, Rebecca C
dc.contributor.authorMarjanovic, Nemanja D
dc.contributor.authorGosik, Kirk
dc.contributor.authorCastano, Ana P
dc.contributor.authorPorter, Caroline BM
dc.contributor.authorLorrey, Selena J
dc.contributor.authorAshenberg, Orr
dc.contributor.authorJerby, Livnat
dc.contributor.authorHofree, Matan
dc.contributor.authorSmith-Rosario, Gabriela
dc.contributor.authorMorris, Robert
dc.contributor.authorGould, Joshua
dc.contributor.authorRiley, Lauren S
dc.contributor.authorBerger, Trisha R
dc.contributor.authorRiesenfeld, Samantha J
dc.contributor.authorRozenblatt-Rosen, Orit
dc.contributor.authorChoi, Bryan D
dc.contributor.authorRegev, Aviv
dc.contributor.authorMaus, Marcela V
dc.date.accessioned2023-01-11T16:49:30Z
dc.date.available2023-01-11T16:49:30Z
dc.date.issued2020
dc.identifier.urihttps://hdl.handle.net/1721.1/147057
dc.description.abstractT cells engineered to express chimeric antigen receptors (CARs) targeting CD19 have produced impressive outcomes for the treatment of B cell malignancies, but different products vary in kinetics, persistence, and toxicity profiles based on the co-stimulatory domains included in the CAR. In this study, we performed transcriptional profiling of bulk CAR T cell populations and single cells to characterize the transcriptional states of human T cells transduced with CD3ζ, 4-1BB-CD3ζ (BBζ), or CD28-CD3ζ (28ζ) co-stimulatory domains at rest and after activation by triggering their CAR or their endogenous T cell receptor (TCR). We identified a transcriptional signature common across CARs with the CD3ζ signaling domain, as well as a distinct program associated with the 4-1BB co-stimulatory domain at rest and after activation. CAR T cells bearing BBζ had increased expression of human leukocyte antigen (HLA) class II genes, ENPP2, and interleukin (IL)-21 axis genes, and decreased PD1 compared to 28ζ CAR T cells. Similar to previous studies, we also found BBζ CAR CD8 T cells to be enriched in a central memory cell phenotype and fatty acid metabolism genes. Our data uncovered transcriptional signatures related to costimulatory domains and demonstrated that signaling domains included in CARs uniquely shape the transcriptional programs of T cells. Maus, Regev, and colleagues performed a deep transcriptional analysis of CAR T cells bearing different signaling domains, at rest and after activation. Findings include CAR-specific signatures and a distinct program activated in CARs with 4-1BB domains that was characterized by expression of central memory markers, MHC class II, and IL-21, among others.en_US
dc.language.isoen
dc.publisherElsevier BVen_US
dc.relation.isversionof10.1016/J.YMTHE.2020.07.023en_US
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivs Licenseen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.sourceElsevieren_US
dc.titleA Distinct Transcriptional Program in Human CAR T Cells Bearing the 4-1BB Signaling Domain Revealed by scRNA-Seqen_US
dc.typeArticleen_US
dc.identifier.citationBoroughs, Angela C, Larson, Rebecca C, Marjanovic, Nemanja D, Gosik, Kirk, Castano, Ana P et al. 2020. "A Distinct Transcriptional Program in Human CAR T Cells Bearing the 4-1BB Signaling Domain Revealed by scRNA-Seq." Molecular Therapy, 28 (12).
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biology
dc.contributor.departmentKoch Institute for Integrative Cancer Research at MIT
dc.contributor.departmentHoward Hughes Medical Institute
dc.relation.journalMolecular Therapyen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dc.date.updated2023-01-11T16:33:06Z
dspace.orderedauthorsBoroughs, AC; Larson, RC; Marjanovic, ND; Gosik, K; Castano, AP; Porter, CBM; Lorrey, SJ; Ashenberg, O; Jerby, L; Hofree, M; Smith-Rosario, G; Morris, R; Gould, J; Riley, LS; Berger, TR; Riesenfeld, SJ; Rozenblatt-Rosen, O; Choi, BD; Regev, A; Maus, MVen_US
dspace.date.submission2023-01-11T16:33:10Z
mit.journal.volume28en_US
mit.journal.issue12en_US
mit.licensePUBLISHER_CC
mit.metadata.statusAuthority Work and Publication Information Neededen_US


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